We are investigating the control mechanisms that regulate the quantity and type of collagen synthesized by cartilage cells in organ and cell culture. In vivo experiments using rabbits will look at the age related changes and compare our findings to what we see in tissue culture using chondrocytes at different passages. Work from our laboratory and others has shown that chondrocytes in culture lost their specificity and instead of synthesizing type II collagen exclusively as they do in the organ environment, begin to synthesize significant amounts of alpha 2 chains which reflect the presence of type I collagen. In addition, as communicated in our progress report (Cheung, et al), we have observed that these chondrocytes in culture begin to express other collagen phenotypes in large amounts, including type III and an unidentified peak, which we have called peak chi, which is pepsin insensitive, has a OHpro/Pro ratio of 1.03, and is sensitive to our highly purified bacterial collagenase. Since we feel that this peak, identified in culture may also be present in diseases of the joint (Osteoarthritis and probably R.A.), we plan to investigate this question. If so, we shall pursue its possible role as an antigen, with the assumption that it may be a triggering factor of an autoimmune process. The effects of compounds such as lymphokines, Vitamin A, lysosomal stabilizers and labelizers will be looked at. The information gathered in this connection should be of great value in understanding the pathogenesis of osteoarthritis. It may shed some light on why chondrocytes do not repair cartilage lesions adequately, and may suggest a means of activating their metabolism. We may learn how to preserve the phenotypic expression and prevent their "dedifferentiation" in culture and in vivo.